Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus

Nature 431, 703-707, 2004

Speaker：李昭鋐                        Time：15：00~16：00, Nov. 17, 2004

Commentator：蕭璦莉 老師                               Place：Room 601

Abstract：

  No other infectious disease is so devastating as the 1918 influenza pandemic. It infected 500 million people and claimed more than 20 million lives. Thus, it is interesting to investigate why this virus strain is so deadly. In this report, the authors used reverse genetics¹ to generate recombinant viruses, containing the viral haemagglutinin (HA) and neuraminidase (NA) genes of the 1918 strain. They demonstrate that the HA of the 1918 strain would enhance pathogenicity in BALB/C mice because the recombinant virus with HA gene of the 1918 virus would cause severe infection in entire lung. They detected high levels of macrophage-derived chemokines and cytokines in lungs of mice infected with recombinant virus. They hypothesized that the unusual burst of pandemic disease may be due to the mutation of HA gene, so the HA proteins would preferentially recognize receptor of human respiratory epithelia. Using a competitive binding assay, they proved that the HA proteins of the 1918 virus preferentially recognized NeuAca-2,6Gal than NeuAca-2,3Gal. In addition, the pre-existing immunity to the virus is also a crucial factor influencing the severity of an influenza pandemic. For example, people who were alive in 1918 had higher neutralization activities against recombinant virus which contains virulent HA gene. Over all, these experiments showed that the HA protein from the 1918 virus is essential for highly lethal infection in an animal model. Hopefully, a better understanding the high virulence of the 1918 influenza virus can help humans to improve global surveillance networks for influenza viruses.

References：

1. Neumann, G. et al. Generation of influenza A viruses entirely from cloned cDNAs. Proc. Natl Acad. Sci. USA 96, 9345–9350 (1999)

2. Darwyn Kobasa et al. Enhanced virulence of influenza A viruses with the

haemagglutinin of the 1918 pandemic virus. Nature 431, 703-707 (2004)